Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism

Imbert, Laurent; Cojean, Sandrine; Libong, Danielle; Chaminade, Pierre; Loiseau, Philippe M.

doi:10.1016/j.biopha.2014.08.009

Cited by 9 publications

(3 citation statements)

References 12 publications

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“…Similarly, proteomic profiles of sitamaquine-resistant isolates suggested for altered profiles of sterol and phospholipid metabolisms have been shown to be related to alterations in phosphatidylethanolamine-N-methyl-transferase and choline kinase activities, leading to decreased cholesterol uptake and ergosterol biosynthesis [179].…”

Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

Sundar

Singh

2018

Expert Review of Proteomics

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Leishmania spp. are causative agents of leishmaniasis, a broad-spectrum neglected vector-borne disease. Genomic and transcriptional studies are not capable of solving intricate biological mysteries, leading to the emergence of proteomics, which can provide insights into the field of parasite biology and its interactions with the host. Areas covered: The combination of genomics and informatics with high throughput proteomics may improve our understanding of parasite biology and pathogenesis. This review analyses the roles of diverse proteomic technologies that facilitate our understanding of global protein profiles and definition of parasite development, survival, virulence and drug resistance mechanisms for disease intervention. Additionally, recent innovations in proteomics have provided insights concerning the drawbacks associated with conventional chemotherapeutic approaches and Leishmania biology, host-parasite interactions and the development of new therapeutic approaches. Expert commentary: With progressive breakthroughs in the foreseeable future, proteome profiles could provide target molecules for vaccine development and therapeutic intervention. Furthermore, proteomics, in combination with genomics and informatics, could facilitate the elimination of several diseases. Taken together, this review provides an outlook on developments in Leishmania proteomics and their clinical implications.

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Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

Sundar

Singh

2018

Expert Review of Proteomics

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“…Its mechanism of action affects the mobility, morphology and growth of the protozoans, through electrostatic interaction between polar ionic groups of the phospholipids present in the parasite membrane and positive charge of the drug [4,27]. It is a new medicine, which is currently in phase II clinical trials in India and Kenya, presenting promising results for oral use [27]. The worst problem with this drug is the poor knowledge of the toxicity of its metabolic [4].…”

Section: Introductionmentioning

confidence: 99%

A review of current treatments strategies based on paromomycin for leishmaniasis

Matos

Viçosa

Ré

et al. 2020

Journal of Drug Delivery Science and Technology

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Leishmaniasis is a neglected disease caused by protozoan parasites of the Leishmania genus, which affects many people in several countries. This disease has three major clinical forms: cutaneous, mucocutaneous and visceral. The current treatments consist of an intravenous, intralesional or intramuscular administration of pentavalent antimonials, but other drugs can be used, among them, amphotericin B, pentamidine, paromomycin and miltefosine. However, these therapies have many side effects. Hence, there is an increase of studies searching for new formulations using different technologies and different routes of administration for leishmaniasis treatment. Paromomycin sulfate (PM) is an aminoglycoside antibiotic, belonging to class III of biopharmaceutical classification system, used intravenously and topically with leishmanicidal activity. This review will provide a general overview of PM current leishmaniasis treatments and new PM formulations. Treatments using PM are available in ointments or creams for topical administration and PM solution for intramuscular administration. The topical treatment with PM presents low efficacy, probably related to low drug permeability across the skin. To improve PM permeability and efficacy, researchers are establishing micro and nanotechnologies. However, further studies are still required to investigate more physicochemical properties and in vitro/in vivo parameters.

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“…sterol 14αdemethylase (14α-DM; EC1.14.13.70) have been described as essential for parasite development [18][19][20][21] . Further, changes in the composition and proportion of sterols in most drug-resistant parasites, even with molecular targets unrelated to sterol biosynthesis, point towards this pathway having an essential role in developing drug resistance [22][23][24][25][26][27][28] particularly in the biosynthesis of membrane phospholipids of Leishmania parasites [29][30][31] . Thus we hypothesise that the link between selection of resistant parasites and metabolic and genetic plasticity suggest that inhibitors that simultaneously target these biosynthetic pathways could be effective anti-leishmanials, particularly against drug resistant Leishmania parasites.…”

Section: Introductionmentioning

confidence: 99%

Drug combinations as effective anti-leishmanials against drug resistant Leishmania mexicana

et al. 2020

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Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism

Cited by 9 publications

References 12 publications

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

A review of current treatments strategies based on paromomycin for leishmaniasis

Drug combinations as effective anti-leishmanials against drug resistant Leishmania mexicana

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